Carcinogenicity of 2,2′-Dihydroxy-di-n-propylnitrosamine in the Tree Shrew (Tupaia glis): Light and Electron Microscopic Features of Pulmonary Adenomas2

Abstract

The carcinogenic effect of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) was examined in the primitive primate, tree shrew (Tupaia glis). DHPN was administered at a dose of 250 mg/kg body weight sc once a week for 80 weeks. Between 65 and 102 weeks, 8 of 9 males given DHPN (89%) and 11 of 14 females given DHPN (78%) developed pulmonary adenomas. In 2 DHPN-treated males, in addition to adenomas, bronchioalveolar carcinomas were observed. Transmission electron microscopic examination of pulmonary adenomas from 4 DHPN-treated animals showed that Clara cells were the main components of these tumors. In addition to pulmonary tumors, 9% of the DHPN-treated animals developed squamous cell carcinomas of the skin and hepatocellular carcinomas. None of the 6 controls, which received olive oil alone, developed any tumors.

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

“…At the time of this study, while HCC [36,37] and pulmonary adenomas [12] were successfully induced by chemical carcinogens in tree shrews, there have been no reports of successful breast cancer. Likewise, without established inbred tree shrews and well-tested transgenic techniques for tree shrews, we opted to attempt inducing breast cancers using conventional chemical, physical or biological methods.…”

“…Accordingly, tree shrews have been successfully used as animal models for human HCC [11] and pulmonary adenomas [12], but there has been no established breast cancer model to date. Using 7,12-dimethylbenz(a)anthracene (DMBA), a strong carcinogen that selectively induced mammary tumours in several rodent animal models [13] may, however, prove effective in developing such a tree shrew breast cancer model.…”

树鼩——作为一种新颖的非人灵长类实验疾病动物模型

“…The first spontaneous lung tumor in the tree shrew was reported in 1996 (Brack et al, 1996). The administration of DHPN (2, 2'-dihydroxy-di-n-propylnitrosamine) at a weekly dose of 250 mg/kg body weight subcutaneous for 80 weeks resulted in 78%-89% of animals developing pulmonary adenomas between 65 and 102 weeks (Rao & Reddy, 1980). In 2013, we administered a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 100 mg/kg) via intraperitoneal injection to induce lung cancer in tree shrews, but did not find any lesions in the lungs after one year (unpublished data).…”

Toxic effect of chloromycetin on the ultrastructures of the motor neurons of the Chinese tree shrew (Tupaia belangeri)

“…Because of its high reproductive rate, its close relation to primates, and its availability in sufficient numbers, the tree shrew has been used as a laboratory species in a variety of medical research fields, including nutritive metabolism, athletic physiology, responses to stimuli, and effects of acute or chronic pressure (Meyer et al 2000;Fuchs and Flugge 2002). It is being considered to be an appropriate experimental model for human diseases, such as hepatitis A (Zhan et al 1981), hepatitis B (Pang et al 1981), hepatitis C (Xie et al 1998), tumors (Adamson et al 1970;Raddy et al 1976;Rao and Raddy 1980), and calculi (Schwaier 1979). Despite the widespread use of tree shrews in the study of human diseases, no studies have been undertaken to show an association between chloromycetin and neurotoxicity, and no studies to date have been able to show that the effects of chloromycetin on the motor neurons, motor nervous terminals, and red nuclei are toxic.…”